Self-stimulation and amphetamine: tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate.
The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051381:Rats; D012653:Self Stimulation / Q000187:drug effects*
D008774:Methylphenidate; D000661:Amphetamine; D003042:Cocaine; D003913:Dextroamphetamine